Medicinal cannabis in the treatment of hypermobile Ehlers-Danlos syndrome & hypermobility spectrum disorder: real-world evidence from Project Twenty21

<p dir="ltr"><b>Background </b>Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs) are heterogeneous disorders of the connective tissue associated with widespread chronic pain and co-occurring autonomic dysfunction. No disease-specific treatment has been identified. Unlicensed cannabis-based medicinal products (CBMPs) are increasingly prescribed for chronic mental and physical conditions.</p><p dir="ltr"><b>Methods </b>Project Twenty21 is a longitudinal, observational registry study producing real-world evidence on the safety and effectiveness of CBMPs prescribed by specialist consultants at UK-based private clinics. This study reports baseline characteristics and three-monthly follow-up patient-reported health outcomes assessed using clinically validated questionnaires for up to 12 months in 121 patients with hEDS/HSD enrolled in Project Twenty21.</p><p dir="ltr"><b>Results </b>Co-morbidity was common, with participants reporting a mean of 6.16 ± 3.8 secondary conditions. Prescription opioid analgesic use was reported by 54 participants (45%), with a statistically significant reduction in mean morphine equivalent observed between baseline and three-month follow-up ( p < 0.001). Statistically significant improvements in mood/depression ( p = 0.010) and sleep quality ( p = 0.031) were observed between baseline and at each follow-up interval for the 12-month study duration with moderate effect sizes. Statistically significant improvements in quality-of-life ( p = 0.001), pain severity ( p < 0.001) and interference ( p < 0.001) were observed at each follow-up interval between baseline and nine-month follow-up with small–moderate effect sizes. Adverse events were reported by six participants (5%) and were predominantly assessed as mild.</p><p dir="ltr"><b>Conclusions </b>CBMP treatment is associated with improved symptomology, quality of life, and functionality in addition to reduced opioid requirement in hEDS/HSD patients. Future research should aim to improve clinical care, mechanistic understanding and refine effective CBMP formulations.</p>